POS0834 LONG-TERM EXTENSION STUDY OF THE SAFETY AND EFFICACY OF NEUROIMMUNE MODULATION USING A VAGUS NERVE STIMULATION DEVICE IN PATIENTS WITH RHEUMATOID ARTHRITIS
Authors: N. Gaylis, D. Sikes, A. Kivitz, D. M. Horowitz, M. Evangelista, Y. Levine, D. Chernoff, M. C. Genovese
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> The inflammatory reflex is a centrally integrated physiological mechanism whereby vagus nerve signaling regulates the production of proinflammatory cytokines that mediate systemic inflammation. The safety and efficacy of a neuroimmune modulation device were assessed in a first-in-human, double-blind pilot study in subjects with multi-drug refractory rheumatoid arthritis (RA). Previously reported data showed that vagus nerve stimulation (VNS) for 12 weeks using the neuroimmune modulation device, a miniature, leadless neurostimulator that is surgically implanted in the neck on the left vagus nerve, improved clinical outcomes, was safe and well-tolerated.<sup>[1]</sup> We now report 36-month long-term data from this pilot study. <h3>Objectives</h3> Determine the long-term safety and efficacy of neuroimmune modulation using a novel neuroimmune modulation device. <h3>Methods</h3> Subjects (N=14) with active RA and prior insufficient response to ≥2 biological or targeted synthetic (b/ts) DMARDs with ≥2 modes of action were implanted with the neuroimmune modulation device.<sup>[1]</sup> All subjects who completed Week 12 (N=14) were enrolled in an open-label, long-term extension study where subjects continued or if assigned to the sham group, began to receive treatment. Of these subjects, 11 completed 36 months of treatment as follows: VNS for 1 minute either once per day (QD, N=4) or four times per day (QID, N=3); subjects randomized to sham treatment during the first 12 weeks were crossed over to active VNS for 1 minute, randomized to either QD (N=3) or QID (N=1). The addition of a concomitant b/tsDMARD to study treatment was allowed at the discretion of the investigator and the subject. The safety and clinical effectiveness of VNS using the Clinical Disease Activity Index (CDAI) were evaluated. <h3>Results</h3> The 11 subjects completing the Month 36 visit had previously failed, on average, five different agents, with 73% (8/11) having failed a tsDMARD. The average CDAI change from baseline (i.e., initiation of stimulation) for the 11 subjects completing Month 36 was -17.8 (SD 16.3). At Month 36, 64% (7/11) of subjects achieved a CDAI MCID response from baseline (by the 12pt/6pt/1pt criteria<sup>[1]</sup>), of whom two (2) were treated with VNS monotherapy and five (5) were on continuous VNS with concomitant b/tsDMARD. The number of subjects in low disease activity (LDA) increased from 9% (1/11) at baseline to 45% (5/11) at Month 36, while the number of subjects in high disease activity (HDA) decreased from 64% (7/11) at baseline to 36% (4/11) at Month 36. Through Month 36, 81% (9/11) subjects elected to combine VNS with a b/tsDMARD, with 8/11 continuing concomitant b/tsDMARD at Month 36. Two adverse events related to VNS therapy occurred during the long-term follow-up period. These events were non-serious, anticipated, and reported by the same subject. One event was a mild sore throat, and the other was moderate tenderness near the implant site. Both events resolved without sequelae following a reduction in stimulation strength. There were no related infections, surgical revisions, or device explantations. <h3>Conclusion</h3> Despite small numbers, data demonstrate long term use of VNS was safe and effective treatment for RA to maintain or lower disease activity including when added to a b/tsDMARD. <h3>Reference</h3> [1]Genovese MC, et al. The Lancet Rheumatology. 2020 Sep 1;2(9):e527-38. <h3>Acknowledgements:</h3> NIL. <h3>Disclosure of Interests</h3> Norman Gaylis: None declared, David Sikes: None declared, Alan Kivitz: None declared, Diane M Horowitz: None declared, Melissa Evangelista Shareholder of: SetPoint Medical, Employee of: SetPoint Medical, Yaakov Levine Shareholder of: SetPoint Medical, Employee of: SetPoint Medical, David Chernoff Shareholder of: SetPoint Medical, Employee of: SetPoint Medical, Mark C. Genovese: None declared.